Drugs affecting the neuromuscular junction

Question 1

What processes may drugs affect at a cholinergic synapse (presynaptic)?

Answer 1

Synthesis of ACh
Movement of ACh into vesicles
Choline transporter
Exocytosis of vesicles

Question 2

What stops the synthesis of ACh?

Answer 2

Cholinacetyltransferase

Question 3

What stops the transport of ACh into vesicles?

Answer 3

Vesamicol

Question 4

What stops choline transporters?

Answer 4

Hemicholinium

Question 5

What stops exocytosis of vesicles?

Answer 5

Toxins

Question 6

What is botulinum toxin?

Answer 6

Clostridium botulinum
2 subunits:
- 1st binds to presynaptic membrane
- 2nd cleaves proteins involved in exocytosis
Block of cholinergic synapses results in muscle death
Used as wrinkle remover

Question 7

What are the two categories of post-synaptic drugs and what do they act upon?

Answer 7

Non-depolarising
Depolarising
Nicotinic AChR

Question 8

How do non-depolarising drugs work?

Answer 8

Competitive antagonists at nAChRs
Lower endplate potential
Used as an adjunct to anaesthesia

Question 9

Give an example of a non-depolarising drug

Answer 9

D-tubocurarine

Question 10

How do depolarising blockers work?

Answer 10

Agonist at nAChRs
Cause endplate depolarisation
Increases action potentials
Uncoordinated, fine contractions (fasciculations)
Prolonged depolarisation inactivates voltage-gated Na+ channels

Question 11

Name a depolarising blocker

Answer 11

Suxamethonium

Question 12

When are depolarising blockers used?

Answer 12

Brief procedures

Question 13

What breakdown depolarising blockers?

Answer 13

Plasma cholinesterase

Question 14

What are some unwanted affects of depolarising blockers?

Answer 14

Bradycardia
K+ release
Intraocular pressure increases
Prolonged paralysis if enzyme is in short supply

Question 15

What are a phase 1 and 2 block?

Answer 15

Phase 1: Inactivation of Na+ voltage gated channels

Phase 2: Inactivation of nAChRs

Question 16

What is a cholinesterase inhibitor?

Answer 16

Interacts with AChE and plasma cholinesterase
Prevents breakdown of ACh
Enhances synaptic function
Affects other synapses where ACh is the transmitter such as autonomic ganglia and postganglionic parasympathetic nerves

Question 17

Explain how the different interactions of the cholinesterase inhibitor is related to their longevity

Answer 17

Edrophonium interacts with the enzyme ionically and effects last for a few minutes
Neostigmine interacts with the enzymes covalent bonds and effects last for a few hours
Organophosphates phosphorylate the enzyme which is irreversible

Question 18

What are organophosphates used for?

Answer 18

Pesticides

Chemical weapons

Question 19

How do cholinesterase inhibitors and non-depolarising blockers interact?

Answer 19

They reverse the effect of non-depolarising blockers

End plate potential is raised

Question 20

What is myasthenia gravis?

Answer 20

Autoimmune disease
Antibody produced against nicotinic AChR
Muscle weakness
Eventually leads to death

Question 21

When are anticholinesterases needed?

Answer 21

Treatment of myasthenia gravis to increase ACh levels and subsequently improve muscle function